A5053337855- Liver physiology and pathology
- IL-33, ST2, and ILC Pathways
- 3D Printing in Biomedical Research
- Force Microscopy Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Asthma and respiratory diseases
- Pluripotent Stem Cells Research
- Pediatric Hepatobiliary Diseases and Treatments
- Liver Disease Diagnosis and Treatment
- Mechanical and Optical Resonators
- Adipokines, Inflammation, and Metabolic Diseases
- Eosinophilic Esophagitis
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Nanocluster Synthesis and Applications
- Pancreatic function and diabetes
- DNA and Nucleic Acid Chemistry
- Advanced MEMS and NEMS Technologies
- Genetic and Kidney Cyst Diseases
- Phagocytosis and Immune Regulation
- Nanofabrication and Lithography Techniques
- Thermal Regulation in Medicine
- Galectins and Cancer Biology
- Whipple's Disease and Interleukins
- Lipid metabolism and disorders
- Pancreatic and Hepatic Oncology Research
Pfizer (United States)
2019-2024
National Institute of Allergy and Infectious Diseases
2014-2021
National Institutes of Health
2014-2021
Wellcome/MRC Cambridge Stem Cell Institute
2014-2016
Medical Research Council
2014-2016
University of Cambridge
2014-2016
Purdue University West Lafayette
2010-2013
Northwestern University
2013
Increasing evidence suggests that asthma is a heterogeneous disorder regulated by distinct molecular mechanisms. In cross-sectional study of asthmatics varying severity (n = 51), endobronchial tissue gene expression analysis revealed three major patient clusters: TH2-high, TH17-high, and TH2/17-low. TH2-high TH17-high patterns were mutually exclusive in individual samples, their signatures inversely correlated differentially interleukin-13 (IL-13) IL-17A. To understand this dichotomous...
Organoids regenerate human bile ducts Bile carry from the liver and gall bladder to small intestine, where it aids digestion. Cholangiocytes are epithelial cells that line modify as its transported through biliary tree. Chronic diseases involving cholangiocytes account for a large fraction of failure need transplantation. Because donors in short supply, Sampaziotis et al. used organoid technology develop cell-based therapy using tissue (see Perspective by Kurial Willenbring). Cholangiocyte...
Induced pluripotent stem cell derived hepatocytes (IPSC-Heps) have the potential to reduce demand for a dwindling number of primary cells used in applications ranging from therapeutic infusions vitro toxicology studies. However, current differentiation protocols and culture methods produce with reduced functionality fetal-like properties compared adult hepatocytes. We report method maturation IPSC-Heps using 3-Dimensional (3D) collagen matrices compatible high throughput screening. This...
Nonalcoholic fatty liver disease (NAFLD) is now the most common progressive in developed countries and second leading indication for transplantation due to extensive fibrosis it causes. NAFLD progression thought be tied chronic low-level type 1 inflammation originating adipose tissue during obesity; however, specific immunological mechanisms regulating of NAFLD-associated are unclear. To investigate immunopathogenesis more completely, we investigated dysfunction, nonalcoholic steatohepatitis...
Fibroproliferative diseases are driven by dysregulated tissue repair responses and a major cause of morbidity mortality because they affect nearly every organ system. Type 2 cytokine critically involved in repair; however, the mechanisms that regulate beneficial regeneration versus pathological fibrosis not well understood. Here, we have shown type effector interleukin-13 simultaneously, yet independently, directed hepatic compensatory proliferation hepatocytes biliary cells progressive...
Background and Aims Organoids provide a powerful system to study epithelia in vitro . Recently, this approach was applied successfully the biliary tree, series of ductular tissues responsible for drainage bile pancreatic secretions. More precisely, organoids have been derived from ductal tissue located outside (extrahepatic ducts; EHBDs) or inside liver (intrahepatic IHBDs). These share many characteristics, including expression cholangiocyte markers such as keratin (KRT) 19. However,...
Persistent or dysregulated IL-13 responses are key drivers of fibrosis in multiple organ systems, and this identifies cytokine as an important therapeutic target. Nevertheless, the mechanisms by which blockade leads to amelioration remain unclear. Because IFN-γ exhibits potent anti-fibrotic activity, IL-4Rα signalling antagonizes effector function, compensatory increases activity following IL-13/IL-4Rα might contribute reduction fibrosis. To investigate role IFN-γ, we developed novel...
There continues to be a major need for more effective inflammatory bowel disease (IBD) therapies. IL-13Rα2 is decoy receptor that binds the cytokine IL-13 with high affinity and diminishes its STAT6-mediated effector functions. Previously, we found was necessary IBD in mice deficient anti-inflammatory IL-10. Here, tested first time therapeutic antibody specifically targeting IL-13Rα2. We also used Il13ra2−/− dissect role of pathogenesis recovery. were modestly protected from induction...
Label-free studies carried out under aqueous phase conditions quantify the number of Mg(2+) ions binding to surface-immobilized T40 sequences, subsequent reordering DNA on surface, and consequences for DNA-DNA interactions. Second harmonic generation measurements indicate that, within error, 18-20 are bound strand at saturation that metal-DNA interaction is associated with a near 30% length contraction strand. Structural reordering, evaluated using vibrational sum frequency generation,...
Metallic and superparamagnetic DNA-templated nanoparticle (NP) chains are examined as potential imaging agents. Proton relaxation times (T1 T2) measured for DNA nanostructures using nuclear magnetic resonance (NMR) spectroscopy. The layer-by-layer (LBL) method was used to encapsulate the NP demonstrated a change in proton times. Results from this study suggest that LBL-coated, can serve effective agents (MRI) applications.
Abstract Fibroproliferative diseases affect a significant proportion of the world's population. Despite this, core mechanisms driving organ fibrosis diverse etiologies remain ill defined. Recent studies suggest that integrin‐alpha V serves as master driver in multiple organs. Although contribute to progression fibrosis, TGF‐β and IL‐13 have emerged central mediators during type 1/type 17, 2 polarized inflammatory responses, respectively. To investigate if interactions or signaling is...
We examine the effects on transverse proton relaxivity after layer-by-layer encapsulation of one-dimensional (1D), DNA templated nanostructures for potential applications as magnetic resonance imaging contrast agents. Multicomponent made with gold−iron oxide and gold−cobalt iron were electrostatically encapsulated by polyelectrolytes (PSS PAH) ligands (RGD peptide) in order to stabilize nanostructure. Transverse was measured 300 MHz H1 nuclear (NMR) spectroscopy. The results indicate that...
Rationale and Objectives Fibrosis is characterized by progressive replacement of normal tissue extracellular matrix. Diagnosis relies on biopsies as noninvasive methods for detection quantification fibrosis are still limited. This work aimed to address the ability 2 molecular magnetic resonance (MR) probes, EP-3533 Gd-Hyd, identify fibrogenesis, respectively, independently presence underlying inflammation in a mouse model chronic liver disease caused infection with Schistosoma mansoni ....
Abstract Longitudinal and transverse relaxation times of multicomponent nanoparticle (NP) chains are investigated for their potential use as multifunctional imaging agents in magnetic resonance (MRI). Gold NPs (ca. 5 nm) arranged linearly along double‐stranded DNA, creating gold NP chains. After cutting with restriction enzymes (EcoRI or BamHI), formed through a ligation reaction enzyme‐cut, superparamagnetic We evaluate the changes different constructs gold–iron oxide gold–cobalt iron using...
Atomic force microscope tips terminated with spore cells are used to directly pattern onto glass and tissue surfaces. The act as sponges eliminate the need use microfabricated ink reservoirs during lithography.
We report a system based on combination of micromanipulator and cantilever-based differential resonator for selecting weighing individual micro-scale particles. Instead relying probabilistic attachment particles sensor surfaces, the can specifically select weigh micro-entities. The is able to move from native media surface that with pg-level resolution. allows individually manipulating wide variety entities be visualized under microscope, ranging cell spheres spore clusters single diatom algae.
An increased incidence of dilated cardiomyopathy and atrial thrombosis was noted in a breeding colony BALB/c mice deficient IL4 receptor α. The condition affected both sexes various ages, extensive testing (microbiology, serology, histopathology) failed to ascertain the cause. Transmission electron microscopy heart samples showed structural defects myocardial intercalated disks, characterized by unorganized heavily convoluted arrangement with lower density less prominent desmosomes adherens...
A composite material consisting of Bacillus subtilis spores suspended in a humidity sensitive hydrogel can be used to pattern biomolecules different concentrations directly onto glass surfaces using mechanical micromanipulator. By altering the relative surrounding gel during deposition, surface concentration patterned controlled and varied create user-defined, biomolecular concentrations.
Abstract Background Inflammation is a hallmark of cachexia; however, effective anti‐inflammatory treatments have not yet been identified. Interleukin‐1 receptor‐associated kinase 4 (IRAK4) key signalling node linking interleukin‐1 receptor (IL‐1R) and toll‐like (TLR) activation to the production multiple proinflammatory cytokines that are elevated in cancer cachexia. The purpose this work evaluate whether pharmacological inhibition IRAK4 activity with PF‐06426779 could prevent cachexia using...